PRMT1 promotes pancreatic cancer development and resistance to chemotherapy.

1. Cell Rep Med. 2024 Mar 19;5(3):101461. doi: 10.1016/j.xcrm.2024.101461. Epub 2024 Mar 8. PRMT1 promotes pancreatic cancer development and resistance to chemotherapy. Ku B(1), Eisenbarth D(2), Baek S(1), Jeong TK(1), Kang JG(1), Hwang D(1), Noh MG(3), Choi C(3), Choi S(1), Seol T(1), Kim H(4), Kim YH(5), Woo SM(5), Kong SY(6), Lim DS(7). Author information: (1)National Creative Research Center for Cell Plasticity, KAIST Stem Cell Center, Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea. (2)National Creative Research Center for Cell Plasticity, KAIST Stem Cell Center, Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea; Brown Center for Immunotherapy, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. (3)Department of Pathology, Chonnam National University Medical School and Hwasun Hospital, Hwasun-gun, Jeonnam 58128, Republic of Korea. (4)Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea. (5)Research Institute, National Cancer Center, Goyang 10408, Republic of Korea. (6)Targeted Therapy Branch, Division of Rare and Refractory Cancer, Research Institute, National Cancer Center, Goyang 10408, Republic of Korea. (7)National Creative Research Center for Cell Plasticity, KAIST Stem Cell Center, Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea. Electronic address: daesiklim@kaist.ac.kr. Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal types of cancer, and novel treatment regimens are direly needed. Epigenetic regulation contributes to the development of various cancer types, but its role in the development of and potential as a therapeutic target for PDAC remains underexplored. Here, we show that PRMT1 is highly expressed in murine and human pancreatic cancer and is essential for cancer cell proliferation and tumorigenesis. Deletion of PRMT1 delays pancreatic cancer development in a KRAS-dependent mouse model, and multi-omics analyses reveal that PRMT1 depletion leads to global changes in chromatin accessibility and transcription, resulting in reduced glycolysis and a decrease in tumorigenic capacity. Pharmacological inhibition of PRMT1 in combination with gemcitabine has a synergistic effect on pancreatic tumor growth in vitro and in vivo. Collectively, our findings implicate PRMT1 as a key regulator of pancreatic cancer development and a promising target for combination therapy. Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.xcrm.2024.101461 PMCID: PMC10983040 PMID: 38460517 [Indexed for MEDLINE] Conflict of interest statement: Declaration of interests The authors declare no competing interests.